Departmento de Química Orgánica, Universidad de Valencia, 46100 Burjassot, Valencia, Spain.
Chemistry. 2012 Mar 19;18(12):3753-64. doi: 10.1002/chem.201102351. Epub 2012 Feb 14.
The preparation of optically pure quaternary piperidines, both fluorinated and non-fluorinated, has been achieved from a chiral imino lactone derived from (R)-phenylglycinol. In the case of the fluorinated derivatives, the addition of (trifluoromethyl)trimethylsilane (TMSCF(3)) followed by iodoamination and migration of the CF(3) group allowed access to four derivatives of α-(trifluoromethyl)pipecolic acid. A theoretical study of the CF(3)-group rearrangement has been carried out to help establish the reaction mechanism of this uncommon transformation. Moreover, a route to trifluoromethyl-substituted iminosugars was also developed through the diastereoselective dihydroxylation of suitable synthetic intermediates. Conversely, alkylation of the starting substrate and subsequent cross-metathesis and aza-Michael reactions led to α-alkyl derivatives of the target compounds.
光学纯季铵型哌啶的制备，无论是氟化的还是非氟化的，都可以从（R）-苯甘氨醇衍生的手性亚氨基内酯来实现。对于氟化衍生物，添加（三氟甲基）三甲基硅烷（TMSCF(3)），然后进行碘氨化和 CF(3)基团的迁移，可得到四种α-（三氟甲基）哌啶酸的衍生物。对 CF(3)基团重排进行了理论研究，以帮助确定这种不常见转化的反应机制。此外，还通过合适的合成中间体的立体选择性二羟基化，开发了三氟甲基取代的亚氨基糖的路线。相反，起始底物的烷基化以及随后的交叉复分解和氮杂迈克尔加成反应导致了目标化合物的α-烷基衍生物。
